We will study a possible precursor-product relationship between myelin-like material and myelin by the use of isotope techniques. These methods will also be utilized to study some of the factors which influence the integration of basic protein and proteolipid protein into the developing myelin sheath (e.g. is there a pool of such proteins not yet integrated into the sheath). The turnover of individual myelin proteins and lipids in the mature myelin sheath will be studied; sensitive double label techniques will be used to determine relative turnover rates of different components within the same animal. Following this preliminary work the bulk of our effort will be devoted to comparative studies of the metabolism of the mature myelin sheath in normal animals and perturbed systems; animals with experimental allergic encephalomyelitis; animals with triethyl tin-induced edema, animals made hyperphenylalaninemic, animals given inhibitors of cholesterol synthesis and starved animals. Normal mice and the Quaking mutant will also be studied. A sensitive double label technique, capable of detecting slight differences in relative turnover rates of various myelin components, will be utilized. Peturbations in metabolism of myelin in vivo will be correlated with in vitro enzymatic assays for the biosynthesis of myelin specific lipids. By comparison of normal and pathological systems we hope to gain information concerning the assembly and maintenance of the myelin sheath and study the mechanisms by which it recovers from metabolic insult.